1. Field of the Invention
The present invention relates to the use of a polypeptide (CD27L) for diagnosis of epithelial-related cancers, in particular kidney cancer e.g. renal cell cancer and colorectal cancer, e.g. colon cancers, as well as in methods of treatment of such cancers. Several publications and patent documents are referenced in this application in order to more fully describe the state of the art to which this invention pertains. The disclosure of each of these publications and documents is incorporated by reference herein in its entirety.
Treatment of most cancer types is usually via surgery, chemotherapy, radiotherapy or biological therapy. However, some tumours become refractory to such treatments, as the cancer cells develop resistance to chemotherapy drugs or lose their hormone sensitivity, leading to recurrent or metastatic disease which is often incurable. More recently, attention has focused on the development of immunological therapies (Green et al. (2000) Cancer Treat. Rev. 26, 269-286; Davis (2000) Immunol. Cell Biol. 78, 179-195; Knuth et al. (2000) Cancer Chemother Pharmacol. 46, S46-51; Shiku et al. (2000) Cancer Chemother. Pharmacol. 46, S77-82; Saffran et al. (1999) Cancer Metastasis Rev. 18, 437-449), such as cancer vaccines and monoclonal antibodies (mAbs), as a means of initiating and targeting a host immune response against tumour cells. In 1998, the FDA approved the use of herceptin (Stebbing et al. (2000) Cancer Treat. Rev. 26, 287-290; Dillman (1999) Cancer Biother. Radiopharm. 14, 5-10; Miller et al. (1999) Invest. New Drugs 17, 417-427), a mAb that recognises the erbB2/HER2-neu receptor protein, as a treatment for metastatic breast cancer. In combination with chemotherapy, herceptin has been shown to prolong the time to disease progression, when compared to patients receiving chemotherapy alone (Baselga et al. (1998) Cancer Res. 58, 2825-2831). The identification of other suitable targets or antigens for immunotherapy of other cancers, for example epithelial-derived cancers, has become increasingly important.
Kidney Cancer
There are three main types of kidney cancer—renal cell cancer that develops in the lining of the renal tubules which filter blood, Wilm's Tumor, found mainly in children under 5 years, and transitional cell cancer of the renal pelvis and/or ureter, that develops in the lining of the bladder, ureters or renal pelvis. Respectively they account for approximately 80%, 5% and 7% of all kidney cancer cases.
As kidney cancer grows, it may invade organs near the kidney, such as the liver, colon, or pancreas. When kidney cancer spreads, cancer cells may appear in the lymph nodes. For this reason, lymph nodes near the kidney may be removed during surgery. Kidney cancer may spread and form new cancers, most often in the bones or lungs.
Surgery is the main treatment for kidney cancer. The aim of surgery is to remove all or as much of the cancer as is possible and to ‘stage’ the cancer accurately so that the need for any further treatment can be assessed. In radical nephrectomy, the whole kidney along with the cancer is removed. The adrenal gland, which is attached to the kidney, is also removed along with the fatty tissue surrounding the kidney. Nearby lymph nodes are also removed as this helps the doctors decide which stage the cancer is. In a partial nephrectomy, only the part of the kidney that contains the cancer is removed and is less commonly performed. In some circumstances, removal of secondary metastases may be done to relieve symptoms such as pain. However, it does not usually help in terms of prognosis and will only be attempted if the cancer is easy to get to and surgery can be performed without causing any serious side effects. Arterial embolisation is a procedure done to block the artery of the kidney containing the cancer. This procedure may be done to control a primary tumour which surgery cannot remove or occasionally prior to an operation to make surgery easier.
Radiotherapy is sometimes used instead of surgery for patients who are too ill to undergo a major operation. In some circumstances it may be used to help with symptoms that arise as a result of recurrent or advanced cancers. However, renal cell kidney cancers are not particularly sensitive to radiotherapy and its use is not routine because studies have not shown that it improves prognosis.
Immunotherapeutic treatment most commonly uses cytokines interleukin-2 and interferon-alpha for the treatment of advanced (metastatic) kidney cancer.
Colorectal Cancer
Excluding skin cancers, colorectal cancer is the third most common cancer diagnosed in men and women in the United States. Surgery is the main treatment for colorectal cancer. Radiation therapy is often used after surgery to kill unremoved deposits and to prevent local recurrences. Adjuvant chemotherapy may also be used, with drugs such as Fluorouracil (5-FU), optionally with leucovorin or levamisole, and Irinotecan (CPT-11). There are no generally approved immunotherapeutic drugs for the treatment of colorectal cancer, despite the fact that immunotherapy may offer the greatest potential after surgical resection in the adjuvant setting. Edrecolomab (monoclonal antibody 17-1 A, or Panorex), however, is an adjunctive therapy for colorectal cancer which is in clinical trials in the UK and the US, and which has already been approved in Germany. Identification of new suitable targets or antigens for immunotherapy of colorectal cancer is therefore highly important.